TB Exposure Research Articles

Evaluation of Diagnostic Performance of Three Commercial Interferon-Gamma Release Assays for Mycobacterium tuberculosis

Interferon-gamma release assays (IGRAs) have gained attention for the diagnosis of latent tuberculosis infection (LTBI) due to their higher specificity compared to the tuberculin skin test (TST). However, the IGRA’s performance varies across different populations. This study evaluated the diagnostic performance of three IGRAs (TBF-FIA, TBF-ELISA, and QFT-Plus) in Ghana, comparing them among individuals exposed and unexposed to MTB infection. Conducted in TB clinics across three regions, this prospective and cross-sectional study included healthy individuals with no known TB exposure (unexposed group) and patients with confirmed active TB (exposed group). Blood samples were tested using all three assays as per the manufacturers’ guidelines. The TBF-ELISA showed 3.4% higher sensitivity but 4.6% lower specificity compared to QFT-Plus. The TBF-FIA had sensitivity of 78.5–87.3% and specificity of 82.9–90.0%. These findings indicate that while the three IGRAs offer similar diagnostic accuracy, the variations in specificity and limited data on assays like TBF-FIA require further investigation.

Predictive factors for tuberculous peripheral pulmonary lesions during radial endobronchial ultrasound

BackgroundTuberculosis frequently poses diagnostic challenge when it presents as a peripheral pulmonary lesion (TB-PPL). The growing use of radial endobronchial ultrasound (rEBUS) for PPL biopsy highlights the need to identify predictive factors for TB-PPL, which is crucial for procedure safety. MethodsA six-year retrospective review at our institution on adult patients with TB and malignant-PPL diagnosed from rEBUS procedure from October 1, 2016, to December 31, 2022. Clinical, radiological, procedural, histological and microbiological data were extracted and analysed. Results387 PPLs were included in our cohort, 32 % were TB-PPL and 68 % were malignant-PPL. The median age was 63 (IQR 55–70) years, with the TB-PPL group significantly younger. The median size of the target lesion was 2.90 (IQR 2.26–4.00) cm. The overall rEBUS diagnostic yield was 85.3 %, with a 1.3 % pneumothorax risk. Multivariate analysis identified independent predictors for TB-PPL, including age <60 years (adj OR 2.635), target lesion size <2 cm (adj OR 2.385), upper lobe location (adj OR 2.020), presence of a cavity on pre-procedural CT (adj OR 4.186), and presence of rEBUS bronchogram (adj OR 2.722). These variables achieved an area under the curve of 0.729 (95 % CI 0.673–0.795) with a diagnostic accuracy of 75.49 % (95 % CI 70.68–79.88). ConclusionsDespite non-specific radiological findings in TB-PPL, our study identifies younger age, target lesion size less than 2 cm, upper lobe location, the presence of cavitation, and rEBUS bronchogram were independent clinical predictors for TB-PPL. This prediction model potentially helps mitigate the risk of accidental TB exposure during bronchoscopic procedures. A future prospective cohort study to validate these findings is essential to allow proper triaging of patient planning for rEBUS procedure.

Acute Leukemia and Latent Tuberculosis Infection in Italy: Quantiferon-Tb Test Screening in a Low Tuberculosis Incidence Country.

Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. However, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated. QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between October 2019 and August 2023. We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. During the 46 months of observation, no patients developed TB reactivation. Despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in Italy. This finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy.

Prevalence, incidence and determinants of QuantiFERONTM positivity in South African schoolchildren.

TB control requires the understanding and disruption of TB transmission. We describe prevalence, incidence and risk factors associated with childhood TB infection in Cape Town, South Africa. We report cross-sectional baseline and prospective incidence data from a large trial among primary school children living in high TB burden communities. Prevalent infection was defined as QuantiFERON™-TB Gold Plus (QFT-Plus) positivity as assessed at baseline. Subsequent conversion to QFT-Plus positivity was measured 3 years later among those QFT-Plus-negative at baseline. Multivariable logistic regression models examined factors associated with TB infection. QuantiFERON-positivity at baseline (prevalence: 22.6%, 95% CI 20.9-24.4), was independently associated with increasing age (aOR 1.24 per additional year, 95% CI 1.15-1.34) and household exposure to TB during the participant's lifetime (aOR 1.87, 95% CI 1.46-2.40). QFT-Plus conversion at year 3 (12.2%, 95% CI 10.5-14.0; annual infection rate: 3.95%) was associated with household exposure to an index TB case (aOR 2.74, 95% CI 1.05-7.18). Rates of QFT-diagnosed TB infection remain high in this population. The strong association with household TB exposure reinforces the importance of contact tracing, preventative treatment and early treatment of infectious disease to reduce community transmission.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus.

In China, the prevalence of type 2 diabetes mellitus (T2DM) among diabetic patients is estimated to be between 90%-95%. Additionally, China is among the 22 countries burdened by a high number of tuberculosis cases, with approximately 4.5 million individuals affected by active tuberculosis. Notably, T2DM poses a significant risk factor for the development of tuberculosis, as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis (T2DM-PTB), which has risen from 19.3% to 24.1%. It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature. To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis (T2DM-PTB), as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM. T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group, Simple DM patients presenting to our hospital in the same period were the control group, Controls and case groups were matched 1:2 according to the principle of the same sex, age difference ( ± 3) years and disease duration difference ( ± 5) years, patients were investigated for general demographic characteristics, diabetes-related characteristics, body immune status, lifestyle and behavioral habits, univariate and multivariate analysis of the data using conditional logistic regression, calculate the odds ratio (OR) values and 95%CI of OR values. A total of 315 study subjects were included in this study, including 105 subjects in the observation group and 210 subjects in the control group. Comparison of the results of both anthropometric and biochemical measures showed that the constitution index, systolic blood pressure, diastolic blood pressure and lymphocyte count were significantly lower in the case group, while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group. The results of univariate analysis showed that poor glucose control, hypoproteinemia, lymphopenia, TB contact history, high infection, smoking and alcohol consumption were positively associated with PTB in T2DM patients; married, history of hypertension, treatment of oral hypoglycemic drugs plus insulin, overweight, obesity and regular exercise were negatively associated with PTB in T2DM patients. Results of multivariate stepwise regression analysis found lymphopenia (OR = 17.75, 95%CI: 3.40-92.74), smoking (OR = 12.25, 95%CI: 2.53-59.37), history of TB contact (OR = 6.56, 95%CI: 1.23-35.03) and poor glycemic control (OR = 3.37, 95%CI: 1.11-10.25) was associated with an increased risk of developing PTB in patients with T2DM, While being overweight (OR = 0.23, 95%CI: 0.08-0.72) and obesity (OR = 0.11, 95%CI: 0.02-0.72) was associated with a reduced risk of developing PTB in patients with T2DM. T2DM-PTB patients are prone to worse glycemic control, higher infection frequency, and a higher proportion of people smoking, drinking alcohol, and lack of exercise. Lymphopenia, smoking, history of TB exposure, poor glycemic control were independent risk factors for T2DM-PTB, and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

How predicted temperature and salinity changes will modulate the impacts induced by terbium in bivalves?

The threat of climate change, which includes shifts in salinity and temperature, has generated a global concern for marine organisms. These changes directly impact them and may alter their susceptibility to contaminants, such as terbium (Tb), found in electronic waste. This study assessed how decreased and increased salinity, as well as increased temperature, modulates Tb effects in Mytilus galloprovincialis mussels. After an exposure period of 28 days, Tb bioaccumulation and biochemical changes were evaluated. Results indicated no significant modulation of salinity and temperature on Tb accumulation, suggesting detoxification mechanisms and adaptations. Further analysis showed that Tb exposure alone caused antioxidant inhibition and neurotoxicity. When exposed to decreased salinity, these Tb-exposed organisms activated defense mechanisms, a response indicative of osmotic stress. Moreover, increased salinity also led to increased oxidative stress and metabolic activity in Tb-exposed organisms. Additionally, Tb-exposed organisms responded to elevated temperature with altered biochemical activities indicative of damage and stress response. Such responses suggested that Tb effects were masked by osmotic and heat stress. This study provides valuable insights into the interactions between temperature, salinity, and contaminants such as Tb, impacting marine organisms. Understanding these relationships is crucial for mitigating climate change and electronic waste effects on marine ecosystems.

The epoxiconazole and tebuconazole fungicides impair granulosa cells functions partly through the aryl hydrocarbon receptor (AHR) signalling with contrasted effects in obese, normo-weight and polycystic ovarian syndrome (PCOS) patients

Polycystic ovarian syndrome (PCOS), frequently associated to obesity, is the main reproductive disorder in women in age to procreate. Some evidence suggests that pesticides can result in alterations of the female reproductive system, including polycystic ovary syndrome (PCOS). Here, we detected two fungicides, Tebuconazole (Tb) and Epoxiconazole (Epox) in the soils and waters of French area. Our hypothesis is that these two triazoles could be associated to the etiology of PCOS. We used the human KGN cell line and primary human granulosa cells (hGCs) from different group of patients: normal weight non PCOS (NW), normal weight PCOS (PCOS NW), obese (obese) and obese PCOS (PCOS obese). We exposed in vitro these cells to Tb and Epox from 0 up to 10 mM for 24 and 48 h and analysed cell viability and steroidogenesis. In hGCs NW, cell viability was reduced from 12.5 µM for Tb and 75 µM for Epox. In hGCs NW, Epox decreased progesterone (Pg) and estradiol (E2) secretions and inhibited STAR, HSD3B and CYP19A1 mRNA expressions from 25 µM and increased AHR mRNA expression from 75 µM. Tb exposure also reduced steroid secretion and STAR and CYP19A1 mRNA expressions and increased AHR mRNA expression but at cytotoxic concentrations. Silencing of AHR in KGN cells reduced inhibitory effects of Tb and Epox on steroid secretion. Tb and Epox exposure decreased more steroid secretion in hGCs from obese, PCOS NW and PCOS obese groups than in NW group. Moreover, we found a higher gene expression of AHR within these three groups. Taken together, both Epox and Tb reduced steroidogenesis in hGCs through partly AHR and Tb was more cytotoxic than Epox. These triazoles alter more strongly PCOS and/or obese hGCs suggesting that human with reproductive disorders are more sensitive to triazoles exposure.

Relationship Between Three Risk Factor Of DM-Pulmonary TB Incident At RSI Siti Aisyah Madiun in 2023

Diabetes mellitus is an infectious disease that has three times the risk of developing pulmonary tuberculosis. The purpose of this study was to analyze the relationship between age, body mass index status, and history of TB exposure and the incidence of DM-TB at Siti Aisyah Madiun Islamic Hospital. This research method uses analytic observational research with a case-control. The total respondents in the case group were 32 patients, and the control group had 32 patients for the 2021–2023 period. The research instrument used was a questionnaire and an observation paper. The results of this study were based on age (adj.RR = 5.082, 95% CI: 1.282–20.145, p 0.021), status factor Body Mass Index (BMI) (adj.RR = 0.172, 95% CI: 0.051–0.573, p 0.004), and TB Exposure (p 0,439). The conclusion of this study is that age and BMI status variables have a relationship. So therefore, DM patients should maintain their diet and adopt a healthy lifestyle.

“Factors associated with HIV-TB Co-infection among children receiving antiretroviral therapy in Imo State, Nigeria”

BackgroundNearly 90 % of children living with HIV and tuberculosis are domiciled in Sub-Saharan Africa. Given the paucity of data on TB-HIV co-infection in children, this study aimed to understand the factors associated with co-infection in children receiving antiretroviral therapy (ART) in Imo State, Nigeria. MethodsWe used a matched case-control study design in this study. 30 TB-HIV incident cases and 90 control children living with HIV receiving ART were recruited from selected HIV treatment sites in Imo State with a case-control ratio of 1:3. A structured questionnaire was used to collect information on family size, socioeconomic status, passive smoking, household food security, and household TB exposure. ResultsHaving at least three people living with a child in a room (P = .006, 95 %CI for odds =1.76–28.78), reduced food intake (P=.004, X2 = 8.50). Having a family member living with HIV (P = 0.016, X2 = 5.75) or having symptoms of TB (P = 0.0001, X2 = 50.39) were all found to be significant factors in HIV-TB coinfection in children. The significant factors of passive smoking were the extent to which the respondents think they are exposed to tobacco smoke at home (P = 0.0001, X2 = 24.14), having some members of the family smoke inside the home (P = 0.0001, X2 = 17.57), and having some degree of exposure to tobacco smoke in socialization areas outside the household (P = 0.0001, X2 = 22.80). None of the social-economic status factors assessed in this study were found to be significant for co-infection except those who earn income to support the family (P = 0.023, X2 = 11.36) and the hours of work they do each week (P = 0.038, X2 =6.54). ConclusionAfter this study, household food security, passive smoking, family size, and household TB exposure are associated with TB-HIV co-infection in children.

Clinical Phenotype and Outcomes of Indo-Asian Patients with ANCA-Associated Glomerulonephritis in the North West, UK

ANCA-associated vasculitides (AAV) are rare, autoimmune conditions associated with end-stage kidney disease (ESKD) and mortality. Data have predominately been from White populations of European ancestry although geographical differences are well documented. Few studies have looked at the incidence, phenotype and clinical outcomes of ethnic minority patients, in particular Indo-Asian populations. A two-center, retrospective cohort study was conducted of patients with ANCA-associated glomerulonephritis (AAGN), self-identifying as Indo-Asian in the North West, UK between 2009 and 2023. A control group of White patients was identified from the same databases and recruited consecutively in relation to the original cohort of Indo-Asian patients. A total of 66 patients were included, 24 patients of Indo-Asian ethnicity and a control cohort of 42 patients of White ethnicity. Indo-Asian patients had a lower median age at diagnosis (53.0 vs. 57.5 years, p = 0.15) and there was an increased prevalence of diabetes mellitus (33.3% vs. 4.8%, p = 0.002) and a higher incidence of previous TB exposure (12.5% vs. 0%, p = 0.019). Outcomes including relapse, ESKD and mortality were similar. We demonstrated an increased crude incidence of AAGN in Indo-Asian patients in the UK compared to similar epidemiological studies. Consideration needs to be given to epidemiological and genetic research, achieved by collaboration and broader recruitment in clinical trials.

Prevalence and risk factors of M tuberculosis infection in young people across 14 communities in Zambia and South Africa.

From 2018-2021 the TB Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) project took place in 21 Zambian and South African communities. The TREATS Incidence of TB Infection Cohort Study was conducted in adolescents and young people (AYP), aged 15-24 years in 14 communities. We describe the baseline prevalence and risk factors of Mycobacterium tuberculosis (M. tuberculosis) infection among this cohort and explore the quantitative QFT-Plus interferon gamma (IFN-γ) responses. A random sample of approximately 300 AYP per community were recruited and information on TB/HIV risk factors, TB symptoms and social mixing patterns collected. QuantiFERON TB Gold Plus assay (QFT-Plus) was used to detect M. tuberculosis infection, following manufacturer's instructions. Logistic regression was used to determine factors associated with infection. 5577 eligible AYP were invited to participate across both countries, with 4648 enrolled. QFT-Plus results were available for 4529: 2552(Zambia) and 1977(South Africa). Overall, 47.6% (2156/4529) AYP had positive QFT-Plus results, the prevalence of infection in South Africa being twice that in Zambia (64.7% (1280/1977) vs 34.3% (867/2552) p<0.001). Infection was associated with age, household contact with TB and alcohol in Zambia but showed no associations in South Africa. The antigen tube differential (TB2-TB1>0.6 IU/ml) of the assay at baseline showed no evidence of association with recent TB exposure. The high prevalence of infection in AYP warrants urgent action to address TB control, especially in South Africa. Further research is required to delineate antigen tube responses of the QFT-Plus assay more precisely to fully realise the benefit of the additional TB2 tube in high TB/HIV burden settings.

A-170 Investigation of High Rate of Low Positive Quantiferon-TB Gold Plus Results

Abstract Background Tuberculosis (TB) is a communicable disease, transmitted almost exclusively by cough aerosols carrying pathogens of the M. tuberculosis complex. TB continues to be a major public health threat, causing an estimated 10.4 million new cases and 1.3 million deaths from TB globally in 2016. Many more people may have latent tuberculosis infection (LTBI), which may go undetected without further laboratory investigation. The Quantiferon-TB Gold Plus (QFT-Plus) is an Interferon Gamma Release Assay (IGRA) for the identification of LTBI. It detects the cellular immune response to antigens of M. tuberculosis and represents an indirect marker of M. tuberculosis exposure. In January of 2021, the NorthShore University HealthSystem Core Laboratory transitioned from a reference laboratory ELISA-based QFT-Plus test to an in-house DiaSorin LIAISON® QuantiFERON®-TB Gold Plus test. After implementation, we noticed a higher rate of low positive QFT-Plus results (1.3%–5.4%) in our patient population that we regard as a mixed risk population. The expected percent of low positive results in a mixed risk population is 2%–3%. Objective To determine the potential causes of a higher rate of low positive Quantiferon-TB Gold Plus Results. Methods Forty specimens with Antigen-Nil results between 0.35–1.00 IU/mL using LIAISON® QuantiFERON®-TB Gold Plus reagent from 8/2022–10/2022 were collected for this study. All forty specimens were re-tested using ELISA-based methodology. Patient demographics and medical history were reviewed for any factor that may be responsible for the low positive results. Results Results from the two different methodologies were compared: 28/40 (70%) specimens showed positive results on the DiaSorin LIAISON®-XL platform, but negative results on the ELISA platform. Review of medical history showed that 92% of the sample population had received more than 2 doses of COVID-19 vaccine and 12.5 % had previous COVID-19 infection. 30% had an underlying autoimmune disease, with psoriasis and rheumatoid arthritis being the most common. However, no correlation was found between medical or vaccination history and the QFT-Plus results. Conclusion LIAISON® QuantiFERON®-TB Gold Plus is a Chemiluminescence immunoassay which is more sensitive than ELISA, resulting in an increased number of low positive QFT-Plus results. Physicians need to correlate clinical findings and TB exposure history to the QFT-Plus results when making clinical decisions.

Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context.

Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh.

A Tuberculous Osteomyelitis Late Finding Affected The Fifth Metatarsal

Many studies have reported osteoarticular involvement of tuberculosis, but few cases of tuberculous osteomyelitis of the foot have been reported. We describe a case of tuberculous osteomyelitis affecting the fifth metatarsal bone in a 56- 56- year-old diabetic male patient and review the literature describing clinical manifestations, imaging aspects, and management of skeletal tuberculosis. A 56- year-old male patient presented with severe pain and swelling in his left leg for the past 6 months. He had no history of trauma. He had fever over his two months, had no cough, had lost weight, and had light sweats at night. His pain and swelling did not subside despite oral medication. The patient was diabetic. The patient also had radiating pain from his lower back to his left leg and numbness all over his lower back. Tuberculosis is a widespread problem in Indonesia. It can affect any part of the body. However, the feet are rarely affected. Tuberculosis is on the rise and it is important to recognize the less common symptoms of this disease to allow early diagnosis and successful treatment. In urban areas where TB prevalence is high, there may be no TB exposure or 'typical' symptoms and signs. Radiological features are non-specific, so indicators of high suspicion are required. Patients with suspected risk factors or tuberculosis should have a biopsy to make the diagnosis and start treatment.

Assessing the impact of terbium on Mytilus galloprovincialis: Metabolic and oxidative stress responses

The increasing demand for electric and electronic equipment has led to a rise in potentially hazardous electronic waste, including rare-earth elements (REEs), such as terbium (Tb), which have been already detected in aquatic systems. This study investigated the biochemical effects of anthropogenic Tb on mussels over a 28-day period. The mussels were exposed to different concentrations of Tb (0, 5, 10, 20, 40 μg/L), and biomarkers related to metabolism, oxidative stress, cellular damage, and neurotoxicity were evaluated. Bioaccumulation of Tb in the mussels' tissue increased with exposure concentrations, but the bioconcentration factor remained similar between treatments. Exposure to Tb enhanced glycogen consumption and decreased metabolic capacity which could be seen as a physiological adaptation to limit Tb accumulation. Antioxidant defenses and glutathione S-transferases showed a more complex dose-response, with enzymatic responses increasing until 10 μg/L but then returning to control levels at 20 μg/L. At 40 μg/L, enzymatic responses were also enhanced but to a lower extent than at 10 μg/L. The presence of Tb had clearly an inhibitory effect on biotransformation enzymes such as carboxylesterases in a dose-dependent manner. Likely, thanks to biochemical and physiological adaptations, no cellular damage or neurotoxicity was observed in any treatments, confirming the mussels' ability to tolerate Tb exposure. Nevertheless, prolonged exposure to these concentrations could lead to harmful consequences when facing other environmental stressors, such as misallocating energy resources for growth, reproduction, and defense mechanisms.

1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis.

Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups. We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year. Incidence was estimated across age and risk groups (<5 years; ≥5 years, diagnosed with human immunodeficiency virus [HIV]; ≥5 years, not diagnosed with HIV/unknown, baseline TBI-positive) by logistic or log-binomial regression fitted using generalized estimating equations. Of 1016 HHCs, 850 (83.7%) from 247 households were assessed (median, 51.4 weeks). Among 242 HHCs, 52 tested interferon-gamma release assay-positive, yielding a 1-year 21.6% (95% confidence interval [CI], 16.7-27.4) TBI cumulative incidence. Sixteen of 742 HHCs developed confirmed (n = 5), probable (n = 3), or possible (n = 8) TBD, yielding a 2.3% (95% CI, 1.4-3.8) 1-year cumulative incidence (1.1%; 95% CI, .5-2.2 for confirmed/probable TBD). TBD relative risk was 11.5-fold (95% CI, 1.7-78.7), 10.4-fold (95% CI, 2.4-45.6), and 2.9-fold (95% CI, .5-17.8) higher in age <5 years, diagnosed with HIV, and baseline TBI high-risk groups, respectively, vs the not high-risk group (P = .0015). By 1 year, 4% (21 of 553) of high-risk HHCs had received TPT. TBI and TBD incidence continued through 1 year in rifampin-/multidrug-resistant TB HHCs. Low TPT coverage emphasizes the need for evidence-based prevention and scale-up, particularly among high-risk groups.

Comparing the diagnostic performance of QuantiFERON-TB Gold Plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis

BackgroundQuantiFERON-TB Gold Plus (QFT-Plus) is an important test that has emerged in recent years for detecting TB infection. We conducted a review to compare the sensitivity, specificity and positive rate of QFT-Plus with that of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-cell spot of tuberculosis assay (T-SPOT.TB) and Tuberculin test (TST).MethodsPubMed and Embase were searched, without language restrictions, from 1 January 2015 to 31 March 2022 using “Mycobacterium tuberculosis Infections” and “QuantiFERON-TB-Plus” as search phrases. We estimated the sensitivity from studies of patients with active tuberculosis, specificity from studies of populations with very low risk of TB exposure, and positive rate from studies of high-risk populations. The methodological quality of the eligible studies was assessed, and a random-effects model meta-analysis was used to determine the risk difference (RD). We assessed the pooled rate by using a random-effects model. This study was registered in PROSPERO (CRD 42021267432).ResultsOf 3996 studies, 83 were eligible for full-text screening and 41 were included in the meta-analysis. In patients with active TB, the sensitivity of QFT-Plus was compared to that of QFT-GIT and T-SPOT.TB, respectively, and no statistically differences were found. In populations with a very low risk of TB exposure, the specificity of QFT-Plus was compared with that of QFT-GTI and T-SPOT.TB, respectively, and no statistically differences were found. Two studies were eligible to compare the specificity of the QFT-Plus test with that of the TST test, and the pooled RD was 0.12 (95% CI 0.02 to 0.22). In high-risk populations, 18 studies were eligible to compare the positive rate of the QFT-Plus test with that of the QFT-GIT test, and the pooled RD was 0.02 (95% CI 0.01 to 0.03). The positive rate of QFT-Plus was compared with that of T-SPOT.TB and TST groups, and no statistically differences were found.ConclusionsThe diagnostic performance of QFT-Plus was similar to that of QFT-GIT and T-SPOT.TB, but was slightly more specific than TST.

A systematic review on correlates of risk of TB disease in children and adults

BackgroundTuberculosis (TB) remains one of the leading causes of death in the world. Targeted treatment to prevent progression from TB exposure and infection to disease is a key element of WHO End-TB strategy. A systematic review to identify and develop correlates of risk (COR) of TB disease is timely. MethodEMBASE, MEDLINE, PUBMED were searched using relevant keywords and MeSH terms published between 2000 and 2020 on COR of TB disease in children and adults. Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) framework was used for structuring and reporting of outcomes. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2). Results4105 studies were identified. Following eligibility screening, 27 studies were quality assessed. Risk of bias was high in all studies. Broad variations in COR type, study population, methodology and result reporting were observed. Tuberculin skin test (TST) and interferon gamma release essays (IGRA) are poor COR. Transcriptomic signatures although promising require validation studies to assess wider applicability. Performance consistency of other CORs-cell marker, cytokines and metabolites are much needed. ConclusionThis review identifies the need for a standardized approach to identify a universally applicable COR signature to achieve the WHO END-TB targets.

In the footsteps of Albert Calmette: an ecological study of TB, leprosy and potential exposure to wild-type Mycobacterium bovis.

One hundred years ago, Albert Calmette developed an avirulent strain of Mycobacterium bovis, but there is no evidence that his BCG strain was more immunogenic than wild-type M. bovis. Geographic variations in BCG efficacy remain ill-understood. We hypothesized that exposure to M. bovis through unpasteurized milk might protect against Mycobacterium tuberculosis and Mycobacterium leprae. After excluding high-income countries (with universal milk pasteurization) and microstates, an ecological study comprising 113 countries was conducted. National data were obtained from United Nations agencies and international organizations about milk production per capita (1980-1999) as a proxy for exposure to wild-type M. bovis, TB (2000-2019) and leprosy (2005-2019) incidence, HIV prevalence (2000-2019), human development index (2010), global hunger index (2010), neonatal BCG coverage (1980-1999), urbanization (2000) and temperature (1990-2020). Multiple linear regression analyses were performed using log-transformed variables. For TB, the association differed by region. An inverse association with milk production was seen in regions outside, but not within, sub-Saharan Africa, after adjustment for confounders. The incidence of leprosy was inversely associated with milk production when combining all countries, but the association was stronger in sub-Saharan Africa. Exposure to wild-type M. bovis through unpasteurized milk may provide cross-protection against M. tuberculosis and M. leprae and contribute to geographic disparities in BCG efficacy. This needs to be confirmed by individual-level studies.

Incomplete contact investigation and risk of developing TB among healthcare professionals.

BACKGROUND: Data on the impact of incomplete contact investigation on TB incidence among healthcare professionals (HCPs) after TB exposure are limited.METHODS: This was a prospective cohort study with 2-year follow-up among Thai HCPs exposed to TB to determine TB incidences and factors associated with TB development.RESULTS: Of the 398 HCPs with TB exposure, 367 (92%) participated in the study; 342 HCPs were included in the final analysis; 311 participated in contact investigations; 303 underwent chest X-ray; 252 completed baseline TB and latent TB infection screening using tuberculin skin test (TST); 210 had negative baseline TST; and 45 completed follow-up tests at 3 months. Altogether, 20 HCPs developed TB (2.92/100 person-years). TB incidences in HCPs not participating in or not completing the investigation at any step were higher than in those who completed the evaluation (11.29 and 2.90, respectively, vs. 0/100 person-years; P < 0.05). No participation in contact investigation and no baseline chest X-ray were independent factors associated with TB development (adjusted odds ratio [aOR] 6.7; P < 0.001 and aOR 8.9; P = 0.01, respectively).CONCLUSION: Study findings indicate increased risks of TB development among HCPs not undergoing or not completing contact investigations and underscore the need for interventions to improve contact investigation participation and completeness.